Neurons in the ventral tegmental area (VTA) play a key role in motor learning, and neurological diseases that affect VTA neurons or their targets in the basal ganglia (BG) severely disrupt behavior. Notably, much of our understanding of how the VTA functions in motor learning has relied on paradigms that employ external reward or punishment and involve relatively slow and simple behaviors, such as lever pressing or licking. In contrast, many of our most complex and valued behaviors, such as speech and musical expression, can be learned without external reinforcement, suggesting that their learning is internally reinforced. Further, internally reinforced behaviors such as speech or musicianship require highly complex and rapid motor sequences and are more readily acquired during juvenile sensitive periods. How the VTA interacts with the BG to mediate complex forms of internally and externally reinforced auditory-motor learning remains unknown. Here we propose to identify how the VTA and BG interact to mediate different forms of auditory-motor learning using a novel combination of intersectional genetic methods to selectively ablate VTA neurons, microdialysis, calcium imaging and optogenetic manipulation of VTA terminals and BG neurons combined with rapid and temporally precise behavioral manipulations. These approaches will be used to test the hypothesis that the VTA functions as a ?critic? that evaluates auditory feedback and instructively modifies BG premotor activity, which in turn drives internally and externally reinforced auditory- motor learning. Resolving how VTA-BG circuits mediate these forms of learning are critical issues for understanding motor plasticity in health and disease. In fact, speech pathologies typify various diseases that affect VTA-BG circuitry, while mutations that disrupt dopamine-mediated signaling in the BG also impair vocal learning. Therefore, the proposed research can shed light on the neural circuit mechanisms that enable complex internally and externally reinforced behavioral learning while also revealing how dysfunction in these circuits interferes with the learning and execution of communicative behaviors.
The proposed research will blend high-resolution recordings of brain activity along with genetic manipulations of neurons to determine the neural pathways and mechanisms necessary to the learning of auditory- dependent motor skills. !
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